Genomes and Genes
Gene Symbol: Prkaca
Description: protein kinase, cAMP dependent, catalytic, alpha
Alias: PKCD, Pkaca, cAMP-dependent protein kinase catalytic subunit alpha, PKA C-alpha, sperm cAMP-dependent protein kinase catalytic subunit
- Nolan M, Babcock D, Wennemuth G, Brown W, Burton K, McKnight G. Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility. Proc Natl Acad Sci U S A. 2004;101:13483-8 pubmed..These results define several crucial roles of PKA in sperm cell biology, bringing together both known and unique PKA-mediated events that are necessary for male fertility. ..
- Zhang W, Morris G, Beebe S. Characterization of the cAMP-dependent protein kinase catalytic subunit Cgamma expressed and purified from sf9 cells. Protein Expr Purif. 2004;35:156-69 pubmed
- Howe D, Wiley J, McKnight G. Molecular and behavioral effects of a null mutation in all PKA C beta isoforms. Mol Cell Neurosci. 2002;20:515-24 pubmed..We conclude that Cbeta protein is not essential for neuronal development or function but may play a more subtle role in memory that is modulated by strain-specific genetic modifiers. ..
- Zhong H, Sia G, Sato T, Gray N, Mao T, Khuchua Z, et al. Subcellular dynamics of type II PKA in neurons. Neuron. 2009;62:363-74 pubmed publisher..Therefore, the localization and activity-dependent translocation of type II PKA are important determinants of PKA function. ..
- Desseyn J, Burton K, McKnight G. Expression of a nonmyristylated variant of the catalytic subunit of protein kinase A during male germ-cell development. Proc Natl Acad Sci U S A. 2000;97:6433-8 pubmed..Because protein kinase A is thought to play a pivotal role in sperm motility and capacitation, the distinctive biochemical properties of the unmyristylated Calpha2 may be essential for fertility in the male. ..
- Amieux P, Howe D, Knickerbocker H, Lee D, Su T, Laszlo G, et al. Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo. J Biol Chem. 2002;277:27294-304 pubmed..Our results demonstrate that unregulated PKA activity negatively affects growth factor-mediated mesoderm formation during early mouse development. ..
- Beebe S, Oyen O, Sandberg M, Frøysa A, Hansson V, Jahnsen T. Molecular cloning of a tissue-specific protein kinase (C gamma) from human testis--representing a third isoform for the catalytic subunit of cAMP-dependent protein kinase. Mol Endocrinol. 1990;4:465-75 pubmed
- Webb R, Marshall F, Swann K, Carroll J. Follicle-stimulating hormone induces a gap junction-dependent dynamic change in [cAMP] and protein kinase a in mammalian oocytes. Dev Biol. 2002;246:441-54 pubmed..These experiments show that increases in cAMP in ovarian somatic cells are communicated via gap junctions to the oocyte, where it can lead to a redistribution of the catalytic subunit of PKA. ..
- Moore M, Kanter J, Jones K, Taylor S. Phosphorylation of the catalytic subunit of protein kinase A. Autophosphorylation versus phosphorylation by phosphoinositide-dependent kinase-1. J Biol Chem. 2002;277:47878-84 pubmed
- Vuong B, Lee M, Kabir S, Irimia C, Macchiarulo S, McKnight G, et al. Specific recruitment of protein kinase A to the immunoglobulin locus regulates class-switch recombination. Nat Immunol. 2009;10:420-6 pubmed publisher..We propose that PKA nucleates the formation of active AID complexes specifically on S regions to generate the high density of DNA lesions required for CSR. ..
- Imaizumi Scherrer T, Faust D, Benichou J, Hellio R, Weiss M. Accumulation in fetal muscle and localization to the neuromuscular junction of cAMP-dependent protein kinase A regulatory and catalytic subunits RI alpha and C alpha. J Cell Biol. 1996;134:1241-54 pubmed..In the adult, the C alpha hybridization signal of muscle is weak and homogeneous...
- Zhou X, Wang H, Burg M, Ferraris J. Inhibitory phosphorylation of GSK-3? by AKT, PKA, and PI3K contributes to high NaCl-induced activation of the transcription factor NFAT5 (TonEBP/OREBP). Am J Physiol Renal Physiol. 2013;304:F908-17 pubmed publisher..When activated by high NaCl, PKA, PI3K, and AKT1, but not p38?, increase phosphorylation of GSK-3?-S9, which reduces the inhibitory effect of GSK-3? on NFAT5, and thus contributes to activation of NFAT5. ..
- Hoang T, Fenne I, Cook C, Børud B, Bakke M, Lien E, et al. cAMP-dependent protein kinase regulates ubiquitin-proteasome-mediated degradation and subcellular localization of the nuclear receptor coactivator GRIP1. J Biol Chem. 2004;279:49120-30 pubmed..Taken together, these data demonstrate that GRIP1 is ubiquitinated and degraded through activation of the PKA pathway. This may represent a novel regulatory mechanism whereby hormones down-regulate a nuclear receptor coactivator. ..
- Lefrançois Martinez A, Blondet Trichard A, Binart N, Val P, Chambon C, Sahut Barnola I, et al. Transcriptional control of adrenal steroidogenesis: novel connection between Janus kinase (JAK) 2 protein and protein kinase A (PKA) through stabilization of cAMP response element-binding protein (CREB) transcription factor. J Biol Chem. 2011;286:32976-85 pubmed publisher..Hence, we describe a novel link between PKA and JAK2 by which nuclear JAK2 signaling controls adrenal steroidogenesis by increasing the stability of CREB. ..
- Ma L, Dong F, Zaid M, Kumar A, Zha X. ABCA1 protein enhances Toll-like receptor 4 (TLR4)-stimulated interleukin-10 (IL-10) secretion through protein kinase A (PKA) activation. J Biol Chem. 2012;287:40502-12 pubmed publisher..ABCA1 is known to suppress proinflammatory cytokines...
- Kim A, Yim N, Im M, Jung Y, Liang C, Cho W, et al. Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells. BMC Complement Altern Med. 2013;13:214 pubmed publisher..These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent. ..
- Syin C, Parzy D, Traincard F, Boccaccio I, Joshi M, Lin D, et al. The H89 cAMP-dependent protein kinase inhibitor blocks Plasmodium falciparum development in infected erythrocytes. Eur J Biochem. 2001;268:4842-9 pubmed..Finally, structural considerations suggest that drugs targeting the parasite, rather than the erythrocyte enzyme, might be developed that could help in the fight against malaria. ..
- Barradeau S, Imaizumi Scherrer T, Weiss M, Faust D. Alternative 5'-exons of the mouse cAMP-dependent protein kinase subunit RIalpha gene are conserved and expressed in both a ubiquitous and tissue-restricted fashion. FEBS Lett. 2000;476:272-6 pubmed..Exon 1d and 1e transcripts are found in several tissues, while exon 1c is testis-specific. All five transcripts are in RIalpha-rich tissues: gonads and adrenal glands. ..
- Sluchanko N, Seit Nebi A, Gusev N. Phosphorylation of more than one site is required for tight interaction of human tau protein with 14-3-3zeta. FEBS Lett. 2009;583:2739-42 pubmed publisher..The state of tau3 phosphorylation affects the mode of 14-3-3 binding and by this means might modify tau filament formation. ..
- Groussin L, Bertherat J. Transcriptional regulation by cyclic AMP is essential for development, reproduction and survival: lessons from the transgenic mice. Eur J Endocrinol. 1998;139:571-2 pubmed
- Faul C, Dhume A, Schecter A, Mundel P. Protein kinase A, Ca2+/calmodulin-dependent kinase II, and calcineurin regulate the intracellular trafficking of myopodin between the Z-disc and the nucleus of cardiac myocytes. Mol Cell Biol. 2007;27:8215-27 pubmed..The identification of myopodin as a direct target of PKA, CaMKII, and calcineurin defines a novel intracellular signaling pathway whereby changes in Z-disc dynamics may translate into compartmentalized signal transduction in the heart. ..
- Smith M, Saraceno G, Capani F, Castilla R. Long-chain acyl-CoA synthetase 4 is regulated by phosphorylation. Biochem Biophys Res Commun. 2013;430:272-7 pubmed publisher..Studies in vitro demonstrated that Acsl4 is a substrate of both PKA and PKC and its phosphorylation by these kinases regulates its activity. ..
- Woo N, Abel T, Nguyen P. Genetic and pharmacological demonstration of a role for cyclic AMP-dependent protein kinase-mediated suppression of protein phosphatases in gating the expression of late LTP. Eur J Neurosci. 2002;16:1871-6 pubmed..Inhibition of PP1/2A did not affect early LTP (E-LTP) or basal synaptic transmission in mutant and wildtype slices. Our data show that genetic inhibition of PKA impairs L-LTP by reducing PKA-mediated suppression of PP1/2A. ..
- Kishi M, Kummer T, Eglen S, Sanes J. LL5beta: a regulator of postsynaptic differentiation identified in a screen for synaptically enriched transcripts at the neuromuscular junction. J Cell Biol. 2005;169:355-66 pubmed..Thus, a strategy designed to identify novel synaptic components led to identification of a protein required for assembly of the postsynaptic apparatus. ..
- Zhang L, Zambon A, Vranizan K, Pothula K, Conklin B, Insel P. Gene expression signatures of cAMP/protein kinase A (PKA)-promoted, mitochondrial-dependent apoptosis. Comparative analysis of wild-type and cAMP-deathless S49 lymphoma cells. J Biol Chem. 2008;283:4304-13 pubmed..The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid cells occurs via mitochondrial-mediated events and imply that such apoptosis involves gene networks in multiple biochemical pathways. ..
- Brauner P, Kopecky P, Flachs P, Kuda O, Vorlicek J, Planickova L, et al. Expression of uncoupling protein 3 and GLUT4 gene in skeletal muscle of preterm newborns: possible control by AMP-activated protein kinase. Pediatr Res. 2006;60:569-75 pubmed..Experiments on adult C57BL/6J mice confirmed the relationships between the transcripts and supported the involvement of AMPK in the control of UCP3 gene expression. ..
- Yu Z, Li D, Huang X, Xing X, Yu R, Li Z, et al. Lysophosphatidic acid upregulates connective tissue growth factor expression in osteoblasts through the GPCR/PKC and PKA pathways. Int J Mol Med. 2016;37:468-74 pubmed publisher..These data indicate that LPA increases CCN2 expression through the activation of PKC and PKA. Thus, the regulatory functions of the PKC and PKA pathways are implicated in the LPA-induced increase in CCN2 expression. ..
- Mena Ulecia K, Vergara Jaque A, Poblete H, Tiznado W, Caballero J. Study of the affinity between the protein kinase PKA and peptide substrates derived from kemptide using molecular dynamics simulations and MM/GBSA. PLoS ONE. 2014;9:e109639 pubmed publisher..As an additional benefit, these methods give detailed molecular information that permit the analysis of the atomic forces that contribute to the affinity between protein kinases and their substrates. ..
- Collins S, Uhler M. Characterization of PKIgamma, a novel isoform of the protein kinase inhibitor of cAMP-dependent protein kinase. J Biol Chem. 1997;272:18169-78 pubmed..These results demonstrate that PKIgamma is a novel, functional PKI isoform that accounts for the previously observed discrepancy between PKI activity and PKI mRNA levels in several mammalian tissues. ..
- Zhang Y, Xu L, Lu Q, Liu K, Liu P, Ji F, et al. VASP activation via the G?13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation. PLoS ONE. 2014;9:e93547 pubmed publisher..Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the G?13/RhoA/PKA/VASP pathway. ..
- GarcÃa BermÃºdez J, SÃ¡nchez AragÃ³ M, Soldevilla B, del Arco A, Nuevo Tapioles C, Cuezva J. PKA Phosphorylates the ATPase Inhibitory Factor 1 and Inactivates Its Capacity to Bind and Inhibit the Mitochondrial H(+)-ATP Synthase. Cell Rep. 2015;12:2143-55 pubmed publisher..Overall, we demonstrate the essential function of the phosphorylation of IF1 in regulating energy metabolism and speculate that dephosho-IF1 might play a role in signaling mitohormesis. ..
- Townsend M, Liu Y, Constantine Paton M. Retina-driven dephosphorylation of the NR2A subunit correlates with faster NMDA receptor kinetics at developing retinocollicular synapses. J Neurosci. 2004;24:11098-107 pubmed
- Agustin J, Wilkerson C, Witman G. The unique catalytic subunit of sperm cAMP-dependent protein kinase is the product of an alternative Calpha mRNA expressed specifically in spermatogenic cells. Mol Biol Cell. 2000;11:3031-44 pubmed..The conservation of C(s) throughout mammalian evolution suggests that the unique structure of C(s) is important in the subunit's localization or function within the sperm. ..
- Sananbenesi F, Fischer A, Schrick C, Spiess J, Radulovic J. Mitogen-activated protein kinase signaling in the hippocampus and its modulation by corticotropin-releasing factor receptor 2: a possible link between stress and fear memory. J Neurosci. 2003;23:11436-43 pubmed..These results suggest that modulation of Mek-1/2-dependent signaling by hippocampal CRF2 can be selectively involved in the delayed effects of stress on memory consolidation. ..
- Huang F, Shan J, Reiken S, Wehrens X, Marks A. Analysis of calstabin2 (FKBP12.6)-ryanodine receptor interactions: rescue of heart failure by calstabin2 in mice. Proc Natl Acad Sci U S A. 2006;103:3456-61 pubmed..Furthermore, using wild-type and genetically altered murine models of heart failure induced by myocardial infarction, we show that manipulating the stoichiometry between calstabin2 and RyR2 can restore normal cardiac function in vivo. ..
- Becker J, Walz A, Daube S, Keck C, Pietrowski D. Distinct responses of human granulosa lutein cells after hCG or LH stimulation in a spheroidal cell culture system. Mol Reprod Dev. 2007;74:1312-6 pubmed..Furthermore, this study strongly indicates that the different effects of hCG and LH in the maintenance of the CL may be reasoned in different signal transduction pathways triggered by hCG or LH. ..
- Unal R, Pokrovskaya I, Tripathi P, Monia B, Kern P, Ranganathan G. Translational regulation of lipoprotein lipase in adipocytes: depletion of cellular protein kinase Calpha activates binding of the C subunit of protein kinase A to the 3'-untranslated region of the lipoprotein lipase mRNA. Biochem J. 2008;413:315-22 pubmed publisher
- Reppel M, Sasse P, Piekorz R, Tang M, Roell W, Duan Y, et al. S100A1 enhances the L-type Ca2+ current in embryonic mouse and neonatal rat ventricular cardiomyocytes. J Biol Chem. 2005;280:36019-28 pubmed..We conclude that the Ca2+-binding protein S100A1 augments transsarcolemmal Ca2+ influx via an increase of PKA activity in ventricular cardiomyocytes and hence represents an important regulator of cardiac function. ..
- Kaihara K, Dickson L, Jacobson D, Tamarina N, Roe M, Philipson L, et al. ?-Cell-specific protein kinase A activation enhances the efficiency of glucose control by increasing acute-phase insulin secretion. Diabetes. 2013;62:1527-36 pubmed publisher..Thus, ?-cell PKA activity transduces the cAMP signal to dramatically increase acute-phase insulin secretion, thereby enhancing the efficiency of insulin to control circulating glucose. ..
- Röder I, Strack S, Reischl M, Dahley O, Khan M, Kassel O, et al. Participation of myosin Va and Pka type I in the regeneration of neuromuscular junctions. PLoS ONE. 2012;7:e40860 pubmed publisher..This suggests an important role of myosin Va and PKA type I for the maturation of NMJs in regenerating muscle. ..
- Willis B, Niswender C, Su T, Amieux P, McKnight G. Cell-type specific expression of a dominant negative PKA mutation in mice. PLoS ONE. 2011;6:e18772 pubmed publisher..Activation of the RI?B allele in vivo provides a novel system for the analysis of PKA function in physiology. ..
- Tobimatsu T, Kaji H, Sowa H, Naito J, Canaff L, Hendy G, et al. Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells. Endocrinology. 2006;147:2583-90 pubmed..The canonical Wnt-beta-catenin pathway is likely to be involved in the antiapoptotic actions of PTH by acting through Smad3 in osteoblasts. ..
- Gerlits O, Das A, Keshwani M, Taylor S, Waltman M, Langan P, et al. Metal-free cAMP-dependent protein kinase can catalyze phosphoryl transfer. Biochemistry. 2014;53:3179-86 pubmed publisher..Comparison of these structures reveals conformational and hydrogen bonding changes that might be important for the mechanism of catalysis. ..
- Huang W, Zhou X, Lefebvre V, de Crombrugghe B. Phosphorylation of SOX9 by cyclic AMP-dependent protein kinase A enhances SOX9's ability to transactivate a Col2a1 chondrocyte-specific enhancer. Mol Cell Biol. 2000;20:4149-58 pubmed
- Devkota S, Sung Y, Choi J, Lee J, Ha N, Kim H, et al. Ei24-deficiency attenuates protein kinase C? signaling and skin carcinogenesis in mice. Int J Biochem Cell Biol. 2012;44:1887-96 pubmed publisher..Finally, using Oncomine database we show that Ei24 and EGFR are upregulated in some subsets of human HNSCC. These results suggest that Ei24 is a regulator of the RINCK1-PKC?-EGFR signaling pathway in the development of skin-cancer. ..
- Lim J, Gerhart Hines Z, Dominy J, Lee Y, Kim S, Tabata M, et al. Oleic acid stimulates complete oxidation of fatty acids through protein kinase A-dependent activation of SIRT1-PGC1? complex. J Biol Chem. 2013;288:7117-26 pubmed publisher..Pharmacological manipulation of this lipid signaling pathway might provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation. ..
- Cummings D, Edelhoff S, Disteche C, McKnight G. Cloning of a mouse protein kinase A catalytic subunit pseudogene and chromosomal mapping of C subunit isoforms. Mamm Genome. 1994;5:701-6 pubmed..This is displaced from its functional homologs, C alpha and C beta, which we map to mouse Chrs 8 (band C3) and 3 (band H3), respectively. ..
- Briassoulis G, Keil M, Naved B, Liu S, Starost M, Nesterova M, et al. Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects reveal the critical role of PKA's catalytic subunits in anxiety. Behav Brain Res. 2016;307:1-10 pubmed publisher..mouse, a Prkar1a heterozygote (Prkar1a(+/-)) mouse with haploinsufficiency for the regulatory subunit (R1Î±), a Prkaca heterozygote (Prkaca(+/-)) mouse with haploinsufficiency for the catalytic subunit (CÎ±), and a double ..
- Hildesheim J, Salvador J, Hollander M, Fornace A. Casein kinase 2- and protein kinase A-regulated adenomatous polyposis coli and beta-catenin cellular localization is dependent on p38 MAPK. J Biol Chem. 2005;280:17221-6 pubmed
- Ryu H, Lee J, Impey S, Ratan R, Ferrante R. Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons. Proc Natl Acad Sci U S A. 2005;102:13915-20 pubmed..These results suggest that the regulation of mitochondrial function via the mitochondrial PKA and CREB pathways may underlie some of the salutary effects of DFO in neurons. ..
- Han Y, Jin Y, Yum J, Jeong H, Choi J, Yeo C, et al. Protein kinase A phosphorylates and regulates the osteogenic activity of Dlx5. Biochem Biophys Res Commun. 2011;407:461-5 pubmed publisher..These results suggest that PKA activity enhances the osteogenic function of Dlx5, at least in part, through protein stabilization and that BMP-2 regulates the osteogenic function of Dlx5, at least in part, through PKA. ..
- Pringle D, Vasko V, Yu L, Manchanda P, Lee A, Zhang X, et al. Follicular thyroid cancers demonstrate dual activation of PKA and mTOR as modeled by thyroid-specific deletion of Prkar1a and Pten in mice. J Clin Endocrinol Metab. 2014;99:E804-12 pubmed publisher..Mouse models paralleling the development of the stages of human FTC should provide important new tools for understanding the mechanisms of FTC development and progression and for evaluating new therapeutics. ..
- Narayana N, Cox S, Shaltiel S, Taylor S, Xuong N. Crystal structure of a polyhistidine-tagged recombinant catalytic subunit of cAMP-dependent protein kinase complexed with the peptide inhibitor PKI(5-24) and adenosine. Biochemistry. 1997;36:4438-48 pubmed..This glycine-rich loop is thus the most mobile component of the active site cleft, with the tip of the loop being highly sensitive to what occupies the gamma-subsite. ..
- Saito T, Sugimoto N, Ohta K, Shimizu T, Ohtani K, Nakayama Y, et al. Phosphodiesterase inhibitors suppress Lactobacillus casei cell-wall-induced NF-?B and MAPK activations and cell proliferation through protein kinase A--or exchange protein activated by cAMP-dependent signal pathway. ScientificWorldJournal. 2012;2012:748572 pubmed publisher..These results indicate that an increase in intracellular cAMP prevents LCWE induction of pathological signaling pathways dependent on PKA and Epac signaling...
- Engelholm L, Riaz A, Serra D, Dagnæs Hansen F, Johansen J, Santoni Rugiu E, et al. CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma. Gastroenterology. 2017;153:1662-1673.e10 pubmed publisher..protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC...
- Li J, Mao G, Xia G. FSH modulates PKAI and GPR3 activities in mouse oocyte of COC in a gap junctional communication (GJC)-dependent manner to initiate meiotic resumption. PLoS ONE. 2012;7:e37835 pubmed publisher..These experiments show that FSH induces a transient increase in cAMP levels and regulates GJC to control PKAI and GPR3 activities, thereby creating an inhibitory phase. After PDE3A and MAPK activities increase, meiosis resumes. ..
- Nystoriak M, Nieves Cintrón M, Patriarchi T, Buonarati O, Prada M, Morotti S, et al. Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes. Sci Signal. 2017;10: pubmed publisher..2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes. ..
- Bae S, Choi J, Oh Y, Yun S, Ryu S, Suh P. Regulation of phospholipase C-gamma1 by protein kinase A-dependent phosphorylation. Adv Enzyme Regul. 2002;42:195-211 pubmed
- Kim S, Yamazaki M, Shevde N, Pike J. Transcriptional control of receptor activator of nuclear factor-kappaB ligand by the protein kinase A activator forskolin and the transmembrane glycoprotein 130-activating cytokine, oncostatin M, is exerted through multiple distal enhancers. Mol Endocrinol. 2007;21:197-214 pubmed..This study demonstrates that the activation of RankL gene expression by PKA- and gp130-inducers is mediated via common regulatory domains that also served to facilitate the activity of 1,25-(OH)2D3. ..
- Uhler M, Carmichael D, Lee D, Chrivia J, Krebs E, McKnight G. Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1986;83:1300-4 pubmed..mRNA levels for both the C subunit and the type I regulatory subunit in various mouse tissues and cell lines were quantitated and compared by using single-stranded RNA probes prepared with SP6 polymerase. ..
- Schmitt J, Stork P. PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rap1. Mol Cell. 2002;9:85-94 pubmed..This study identifies an antiproliferative role for Src in the physiological regulation of cell growth by cAMP. ..
- Gao Z, Young R, Trucco M, Greene S, Hewlett E, Matschinsky F, et al. Protein kinase A translocation and insulin secretion in pancreatic beta-cells: studies with adenylate cyclase toxin from Bordetella pertussis. Biochem J. 2002;368:397-404 pubmed..In conclusion, glucose and GLP-1 amplify insulin secretion via cAMP production and PKAbeta activation. ..
- Yang J, Wu J, Steichen J, Kornev A, Deal M, Li S, et al. A conserved Glu-Arg salt bridge connects coevolved motifs that define the eukaryotic protein kinase fold. J Mol Biol. 2012;415:666-79 pubmed publisher..Mutations of either residue disrupt communication not only between the two segments but also within the rest of the molecule, leading to altered catalytic activity and enzyme regulation. ..
- Zasłona Z, Scruggs A, Peters Golden M, Huang S. Protein kinase A inhibition of macrophage maturation is accompanied by an increase in DNA methylation of the colony-stimulating factor 1 receptor gene. Immunology. 2016;149:225-37 pubmed publisher..Together, these results demonstrate that macrophage maturation is accompanied by Csf1r hypomethylation, and illustrates for the first time the ability of PKA to increase Csf1r DNA methylation. ..
- Lin J, Chang W, Chen H, Lai H, Chen C, Tao M, et al. Regulation of feedback between protein kinase A and the proteasome system worsens Huntington's disease. Mol Cell Biol. 2013;33:1073-84 pubmed publisher..Collectively, our data demonstrated that positive feedback regulation between PKA and the proteasome is critical for HD pathogenesis. ..
- Gerhart Hines Z, Dominy J, Blättler S, Jedrychowski M, Banks A, Lim J, et al. The cAMP/PKA pathway rapidly activates SIRT1 to promote fatty acid oxidation independently of changes in NAD(+). Mol Cell. 2011;44:851-63 pubmed publisher..These studies support a mechanism of Sirtuin enzymatic control through the cAMP/PKA pathway with important implications for stress responses and maintenance of energy homeostasis. ..
- Hirakis S, Malmstrom R, Amaro R. Molecular Simulations Reveal an Unresolved Conformation of the Type IA Protein Kinase A Regulatory Subunit and Suggest Its Role in the cAMP Regulatory Mechanism. Biochemistry. 2017;56:3885-3888 pubmed publisher..Brownian dynamics simulations suggest that the Flipback conformation plays a role in cAMP association to the A domain of the R subunit. ..
- Morgan D, Weisenhaus M, Shum S, Su T, Zheng R, Zhang C, et al. Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation. Proc Natl Acad Sci U S A. 2008;105:20740-5 pubmed publisher..The conditional CalphaM120A-expressing mouse lines will be valuable tools for studying PKA function in vivo. ..
- Mishra S, Melino G, Murphy L. Transglutaminase 2 kinase activity facilitates protein kinase A-induced phosphorylation of retinoblastoma protein. J Biol Chem. 2007;282:18108-15 pubmed..These data indicate that Rb is a substrate for TG2 kinase activity and suggest that phosphorylation of Rb, which results from activation of PKA in fibroblasts, is indirect and requires TG2 kinase activity. ..
- Xie K, Zhu M, Xiang P, Chen X, Kasimumali A, Lu R, et al. Protein Kinase A/CREB Signaling Prevents Adriamycin-Induced Podocyte Apoptosis via Upregulation of Mitochondrial Respiratory Chain Complexes. Mol Cell Biol. 2018;38: pubmed publisher..We conclude that the upregulation of mitochondrial respiratory chain proteins played a partial role in the protection of PKA/CREB signaling. ..
- Cui C, Zhao H, Zhang Z, Zong Z, Feng C, Zhang Y, et al. CDC25B acts as a potential target of PRKACA in fertilized mouse eggs. Biol Reprod. 2008;79:991-8 pubmed publisherProtein kinase A (PRKACA) has been documented as a pivotal regulator in meiosis and mitosis arrest...
- Schnizler K, Shutov L, Van Kanegan M, Merrill M, Nichols B, McKnight G, et al. Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons. J Neurosci. 2008;28:4904-17 pubmed publisher..Together, these data suggest that PKA anchoring by AKAP150 is essential for the enhancement of TRPV1 function by activation of the PGE(2)/PKA signaling pathway. ..
- Oksvold M, Funderud A, Kvissel A, Skarpen E, Henanger H, Huitfeldt H, et al. Epidermal growth factor receptor levels are reduced in mice with targeted disruption of the protein kinase A catalytic subunit. BMC Cell Biol. 2008;9:16 pubmed publisher..Our results suggest that PKA may represent a target that when manipulated can maintain EGFR protein levels at the single cell level as well as in intact animals. ..
- Li Y, He W, Jha K, Klotz K, Kim Y, Mandal A, et al. FSCB, a novel protein kinase A-phosphorylated calcium-binding protein, is a CABYR-binding partner involved in late steps of fibrous sheath biogenesis. J Biol Chem. 2007;282:34104-19 pubmed..Due to its temporal appearance during spermiogenesis and location at the cortex of the fibrous sheath, FSCB is postulated to be involved in the later stages of fibrous sheath assembly...
- Wilderman A, Guo Y, Divakaruni A, Perkins G, Zhang L, Murphy A, et al. Proteomic and Metabolic Analyses of S49 Lymphoma Cells Reveal Novel Regulation of Mitochondria by cAMP and Protein Kinase A. J Biol Chem. 2015;290:22274-86 pubmed publisher..Together, these findings show that cAMP acts via PKA to regulate multiple aspects of mitochondrial function and structure. Mitochondrial perturbation thus likely contributes to cAMP/PKA-mediated cellular responses. ..
- Wagner S, Dantz C, Flebbe H, Azizian A, Sag C, Engels S, et al. NADPH oxidase 2 mediates angiotensin II-dependent cellular arrhythmias via PKA and CaMKII. J Mol Cell Cardiol. 2014;75:206-15 pubmed publisher..Oxidative activation of PKA and CaMKII via NOX2 may represent important pro-arrhythmogenic pathways in the setting of increased Ang II stimulation, which may be relevant for the treatment of arrhythmias in cardiac disease. ..
- Yamamoto T, Shimano H, Inoue N, Nakagawa Y, Matsuzaka T, Takahashi A, et al. Protein kinase A suppresses sterol regulatory element-binding protein-1C expression via phosphorylation of liver X receptor in the liver. J Biol Chem. 2007;282:11687-95 pubmed
- Robin M, Prabu S, Raza H, Anandatheerthavarada H, Avadhani N. Phosphorylation enhances mitochondrial targeting of GSTA4-4 through increased affinity for binding to cytoplasmic Hsp70. J Biol Chem. 2003;278:18960-70 pubmed..We demonstrate for the first time that PKA and PKC modulate the cytoplasmic and mitochondrial pools of GSTA4-4. ..